1. Field of the Invention
The present invention relates to compositions for preventing and treating of obesity, hyperlipidemia, atherosclerosis, fatty liver, diabetes or metabolic syndrome containing extracts of G. max leaves or fractions isolated from the same.
2. Description of the Related Art
Obesity, one of chronic diseases suffered by modern people, is rising as a serious health-threatening problem in the wave of industrialization and change of diet habit and life style resulted from the increase of income. In 1996, obesity was acclaimed as disease by WHO. Obesity is also known to be related directly or indirectly to adult diseases such as diabetes, hypertension, hyperlipidemia, and heart disease and various types of cancer.
The mechanisms of anti-obesity agents known so far are appetite suppression, thermogenesis acceleration, diuretic action, digestion inhibition, and hormone regulation. Reductil (Reductil™, Abbott, USA), one of the most widely used anti-obesity agents, is an appetite suppressant, which forms over a hundred million dollar market in USA. However, such appetite suppressant therapy for treating obesity has side effects such as hypertension, diarrhea, constipation, insomnia and anxiety. Therefore, it is urgently required to develop a drug for the prevention and treatment of obesity that has less side effects but has excellent stability for long term administration.
With the increase of adult diseases, cardiovascular diseases are recently rising significantly. One of the most representative cardiovascular diseases is atherosclerosis, which is the inflammatory disease progressed by the lipid accumulation and fibrous-cap formation in artery wall. Hypertension, smoking, obesity and the increase of low-density lipoprotein (LDL) seem to be major reasons for atherosclerosis. Atherosclerosis is easily developed in cerebral artery or coronary artery, which progresses to circulatory disease such as heart disease and cerebrovascular disease.
Acyl-CoA:cholesterol acyltransferase (ACAT) plays an important role in esterification of cholesterol. Particularly, ACAT converts cholesterol to its ester form to accumulate cholesterol in cells. The human ACAT exists as two isoenzymes, ACAT-1 and ACAT-2. Human ACAT-1 (50 kDa) works in adult liver, adrenal gland, macrophage and kidney, while human ACAT-2 (46 kDa) works in small intestines (Curr. Opin. Lipidol. 12: 121-127, 2001). ACAT inhibitors can inhibit the absorption of cholesterol taken from food and inhibit the accumulation of cholesteryl ester in vascular endothelial cells, so that it can be a target material for the prevention and treatment of hypercholesterolemia, cholesterol gallstones or atherosclerosis (Nature Med. 6, 1341-1347, 2000).
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an independent risk factor causing coronary artery disease in hypercholesterolemia patients, and is proposed as a pro-inflammatory agent. Lp-PLA2 has been identified in macrophages of atherosclerotic lesions (Arterioscler. Thromb. Vasc. Biol. 19: 2909-2971, 1999). According to recent studies, the administration of Lp-PLA2 inhibitor decreases significantly the fatty streak formation of Watanabe heritable hyperlipidemic rabbit, an atherosclerotic animal model (Atherosclerosis, 151: 166, 2000). Thus, Lp-PLA2 inhibitor has become a target for the prevention and treatment of atherosclerosis (N. Engl. J. Med. 343: 1148-1155, 2000). It is believed that the development of Lp-PLA2 inhibitor is a very important task for the prevention and treatment of atherosclerosis.
Metabolic syndrome is also known as insulin resistance syndrome, which is closely related to obesity, type II diabetes, hypertension, hypertriglyceridemia, hypercholesterolemia, and atherosclerosis. In particular, the reason why metabolic syndrome has been a major concern in our society is that it might cause various vascular diseases caused by atherosclerosis that destroy the quality of life in a patient or make matter worse to cause early death of a patient. Therefore, it is very important to diagnose early and to treat the increasing metabolic syndrome and further to prevent the same.
Soybean (Glycine max (L.) Merr.) is annual plant belonging to the Leguminosae (Fabaceae) family and widely distributed in Asia, Africa, and Australia. This plant has been widely cultivated as edible plant. Soybean is rich in protein and lipid and also contains many bioactive materials, so that it can inhibit the development of coronary heart disease, breast cancer, prostatic cancer, and colon cancer. Studies for the prevention of adult disease using soybean have been undergoing. Soybean root is also a medicinal material used in Korean traditional medicine and folk remedy. The conventional arts in relation to using soybean root are described in Korean Patent No. 500641 relating to food for promoting hair growth, Korean Patent No. 439147 relating to the compositions for care of skin suffering from acne or seborrhea, and Korean Patent Publication No. 2001-0071541 relating to the composition for the prevention and/or treatment of osteoporosis and alterations due to menopause syndrome.
Much research has been devoted to the composition of soybean leaves (G. max leaves). As shown in Table 1 and FIG. 1, the composition of soybean leaves (G. max leaves) is different from that of soybean, soybean stems or roots (Food Sci. Biotechnol. 17: 578-586, 2008; Biomed. Pharmacother. 56: 289-295, 2002; Agric. Chem. Biotechnol. 49: 51-55, 2006; J. Agric. Food Chem. 54. 2057-2063, 2006; Bull. Kor. Chem. Soc. 29: 615-619, 2008).
TABLE 1SoybeanSoybeanCompoundsleavesSoybeanrootsdaidzein∘∘∘(4′,7-dihydroxyisoflavone)genistein∘∘∘(4′,5,7-trihydroxyisoflavone)genistin∘∘ND(4′,5,7-Trihydroxyisoflavone-7-O-β-D-glucopyranoside)glycitein∘∘∘(4′,7-Dihydroxy-6-methoxyisoflavone)6′-O-malonyldaidzin∘∘ND6′-O-malonylgenistin∘∘NDkaempferol-3-O-α-L-∘NDNDrhamnopyranosyl(1→2)-β-D-glucopyranosyl(1→6)-β-D-galactopyranosidekaempferol-3-O-(2,6-di-O-α-∘NDNDrhamnopyranosyl)-β-galactopyranosidekaempferol-3-O-digalactopyranoside∘NDNDKaempferol-3-O-diglucopyranoside∘NDNDkaempferol-3-O-α-L-∘NDNDrhamnopyranosyl(1→6)-β-D-galactopyranosidekaempferol-3-O-rutinoside∘NDND3′,4′,5,7-tetrahydroxyflavone∘NDND3′,4′,5-trihydroxyflavone-7-O-β-D-∘NDNDglucopyranoside3′,4′,5,7-tetrahydroxyflavonol∘NDNDcoumestrol∘∘NDglyceofuran∘∘ND4-hydroxybenzoic acid∘NDNDmethyl-4-hydroxybenzoate∘NDNDsoysapogenol B∘NDNDstigmasterol∘∘NDD-mannitol∘NDND5,7,4′-trihydroxyflavone∘NDNDisoformononetin∘NDND(4′-Hydroxy-7-methoxyisoflavone)3-O-[α-L-rhamnopyranosyl-(1→2)-∘NDND[β-D-glucopyranosyl-(1→6)]-β-D-glucopyranoside]fluorocitric acid∘NDND* ND: not detected
The contents of major components of G. max, isoflavone aglycons and glycosides (Daidzein, Glycitein, Genistein, Genistin, Daidzin, and Glycitin) are significantly decreased in soybean>soybean roots>soybean leaves (G. max leaves) (harvested after at least 90 days of cultivation) in that order (J. Agric. Food Chem. 53: 5848-5852, 2005). Therefore, the composition containing extracts of G. max leaves or fractions isolated from the same as an active ingredient contains other components than isoflavone aglycons and glycosides found in soybean or soybean roots. G. max leaves contain lots of kaempferol glycosides, but the effects of G. max leaves containing kaempferol glycosides has not been reported.
While searching a new anti-obesity agent from natural resources having less side effects, the present inventors figured out that the extracts of G. max leaves or fractions isolated from the same reduce body fat, blood cholesterol, triglyceride, glucose, insulin and hepatoxicity index enzyme level, inhibit the accumulation of fat in liver tissues, and inhibit the formation of artery lesion in cardio artery, so that they can be effectively used for the prevention and treatment of obesity, hyperlipidemia, atherosclerosis, fatty liver, diabetes or metabolic syndrome, leading to the completion of this invention.